Triiodothyronine toxicity

Administered in the drinking water of rats for 100 days, 1, 3, 10, or lOOmg/1 of iodine caused no signs of overt toxicity but some modifications of thyroid function occurred. Specifically, there was a dose-related trend in increased plasma thyroxine levels and a statistically significant increase in the thyroxine-to-triiodothyronine ratio. 

None of these augmentation strategies is ideal, since they either require plasma monitoring (lithium, tryptophan, tri-iodothyronine), expose the patient to potential toxicity (lithium, tryptophan) or have only a moderate evidence base for efficacy (triiodothyronine, pindolol). 

Hyperthyroidism (excessive production of thyroid hormones) asually requires surgery, but before. surgery the patient mu.st be prepared by preliminary abolition of the hyper-thyroidi.sm through the use of antithyroid drugs. Thiourea and related eompounds. show an antithyroid activity, but they arc too toxic for clinical use. The more useful drugs are 2-thiouracil derivatives and a closely related 2-thioimidazolc derivative. All of these appear to have a similar mechanism of action (i.c.. prevention of the iodination of the precursors of thyroxine and triiodothyronine). The main difference in the compounds lies in their relative toxieities. 

Amiodarone may cause asymptomatic corneal microdeposits and inhibit the conversion of thyroxine (T4) to triiodothyronine (T3). Amiodarone has caused pulmonary toxicity (hypersensitivity pneumonitis or intershtial/alveo-lar pneumonihs). It is embryotoxic in that it increases fetal resorphon and causes growth retardation. Amiodarone is excreted in breast milk. 

Other drugs that are useful in the rapid treatment of the severely thyrotoxic patient are agents that inhibit the peripheral conversion of thyroxine to triiodothyronine. Dexamethasone (0.5 to 1 mg two to four times daily), and the iodinated radiological contrast agents iopanoic acid (Telepaque, 500 to 1000 mg once daily), and sodium ipodate (Qragrafin, 500 to 1000 mg once daily) are effective in preoperative preparation. Neither iopanoic acid nor sodium ipodate is available in the United States. Cholestyramine has been used in severely toxic patients to bind thyroid hormones in the gut and thus block the enterohepatic circulation of the iodothyronines. 

Thyroid hormone is available as synthetic triiodothyronine (T3, or liothyronine), synthetic tetraiodothyronine (T4, levothyroxine), or natural desiccated animal thyroid (containing both T3 and T4 Table 11-55). Despite concern over the potentially life-threatening manifestations of thyrotoxicosis, serious toxicity rarely occurs after acute thyroid hormone ingestion. 

A. An acute ingestion of more than 5 mg of levothyroxine (T4) or 0.75 mg of triiodothyronine (T3) is considered potentially toxic. An adult has survived an ingestion of 48 g of unspecified thyroid tablets a 15-month-old child had moderate symptoms after ingesting 1.5 g of desiccated thyroid. 

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